(+)-Cycloserine

102.09

102.09

80798

200-688-4

95IK5KI84Z

756712

DTXSID8022870

C47466

CRYSTALS|WHITE TO PALE YELLOW, CRYSTALLINE POWDER

J - Antiinfectives for systemic use

2934999090

64.4

-1.5

white to off-white powder

1.3±0.1 g/cm3

155-156 °C (decomp)

267ºC

1.475

H2O: soluble

−20°C

111 º (C=5, 2N NaOH)

ODORLESS OR HAS FAINT ODOR

AQ SOLN HAVE PH OF ABOUT 6

FORMS SALT WITH ACIDS OR BASES|HYGROSCOPIC

NONH for all modes of transport

2

5-20

38-36/37-24/25

NY2975000

Xn

UNSTABLE @ ROOM TEMP; STABLE @ 4-5 DEG C.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 5 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Oral LD50 in mouse is 5290 mg/kg, and in rat is over 5000 mg/kg. Symptoms of a cycloserine overdose include drowsiness, confusion, headache, dizziness, irritability, numbness and tingling, difficulty speaking, paralysis, abnormal behavior, seizures, and unconsciousness.

Cycloserine is reported to be associated with a low rate of serum aminotransferase elevations that are usually transient and asymptomatic and do not require dose modification. Cycloserine is usually used in combination with agents that are more clearly linked to liver test abnormalities, and it generally plays little or no role in these abnormalities. Cycloserine has not been definitely linked to instances of clinically apparent liver injury, but is often used with agents that are known hepatotoxins and its possible contribution cannot always be excluded.

ISONIAZID SHOULD NOT BE GIVEN WITH CYCLOSERINE BECAUSE OF POSSIBLE ADDITIVE CENTRAL NERVOUS SYSTEM TOXICITY.|/Cycloserine/ may increase the risk of seizures, especially in chronic alcohol abuse; patients should be advised to avoid concurrent use.|Concurrent use /with isoniazid/ may result in increased incidence of CNS effects such as dizziness or drowsiness; dosage adjustments may be necessary, and patients should be monitored for signs of CNS toxicity.|Cycloserine may cause anemia or peripheral neuritis by acting as a pyridoxine antagonist or increasing renal excretion of pyridoxine; requirements for pyridoxine may be increased in patients receiving cycloserine.

Used in combination with up to 5 other drugs as a treatment for Mycobacterium avium complex (MAC) and is also used to treat tuberculosis (TB).

Cycloserine is a broad spectrum antibiotic used as a second line agent for treatment of drug resistant tuberculosis, always in combination with other antituberculosis agents. Cycloserine is appears to have little or no hepatotoxic potential, but it is usually used in combination with agents that are known to be hepatotoxic, and its role in the reported cases of liver injury with combination therapy cannot always be excluded.

Antituberculosis Agents

Anti-Infective Agents, Urinary; Antibiotics, Antitubercular; Antimetabolites|INHIBITS WIDE VARIETY OF BOTH GRAM-POSITIVE & GRAM-NEGATIVE BACTERIA, INCL MYCOBACTERIA. ... IT HAS BEEN USED SUCCESSFULLY AGAINST STUBBORN URINARY TRACT INFECTIONS CAUSED BY STREPTOCOCCI, STAPHYLOCOCCI, E COLI & AEROBACTER AEROGENES.|Cycloserine is indicated in combination with other antituberculars in the treatment of tuberculosis after failure of the primary medications (pyrazinamide, streptomycin, isoniazid, rifampin, and ethambutol). /Included in US product labeling/|Cycloserine is used in the treatment of atypical mycobacterial infections, such as mycobacterium avium complex. /NOT included in US product labeling/|For more Therapeutic Uses (Complete) data for CYCLOSERINE (6 total), please visit the HSDB record page.

PATIENTS WITH HISTORY OF MENTAL ILLNESS OFTEN TOLERATE CYCLOSERINE UNUSUALLY WELL, WHEREAS APPARENTLY STABLE INDIVIDUALS MAY DEVELOP PSYCHOTIC REACTION SOON AFTER INITIATION OF TREATMENT, SOMETIMES BEFORE THERAPEUTIC SERUM LEVELS ARE ACHIEVED.|Maternal Medication usually Compatible with Breast-Feeding: Cycloserine: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/|The drug may accumulate to toxic concentrations in patients with renal insufficiency; it may be removed from the circulation by dialysis.|Because cycloserine is renally excreted, cycloserine may accumulate in patients with renal function impairment, leading to an increased risk of side effects; the medication should not be given to patients with renal function impairment (creatinine clearance of < 50 ml per minute (0.83 ml per second)).|For more Drug Warnings (Complete) data for CYCLOSERINE (10 total), please visit the HSDB record page.

Cycloserine, a broad-spectrum antibiotic, may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. Cycloserine works by blocking the formation of these peptidoglycans. By doing this the walls of the bacteria become weak and it results in the death of the bacteria

Substances capable of killing agents causing urinary tract infections or of preventing them from spreading. (See all compounds classified as Anti-Infective Agents, Urinary.)|Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic. (See all compounds classified as Antibiotics, Antitubercular.)|Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033) (See all compounds classified as Antimetabolites.)

Rapidly and almost completely absorbed (70 to 90%) from the gastrointestinal tract following oral administration.|VALUE OF CYCLOSERINE IS ENHANCED BY FACT THAT IT DIFFUSES INTO CELLS & CROSSES BLOOD-BRAIN BARRIER, EVEN IN ABSENCE OF DISEASE.|When given orally, 70% to 90% of cycloserine is rapidly absorbed. Peak concentrations in plasma are reached 3 to 4 hours after a single dose and are in the range of 20 to 35 ug/ml in children who receive 20 mg/kg; only small quantities are present after 12 hours.|Cycloserine is distributed throughout body fluids and tissues. There is no appreciable blood-brain barrier to the drug, and CSF concentrations in all patients are approximately the same as those in plasma. About 50% of a parenteral dose of cycloserine is excreted unchanged in the urine in the first 12 hours; a total of 65% is recoverable in the active form over a period of 72 hours.

APPROX 35% OF ANTIBIOTIC IS METABOLIZED TO AS-YET-UNIDENTIFIED SUBSTANCE.

Half-life in patients with normal renal function is 10 hours, and is prolonged in patients with impaired renal function.|Normal renal function - 10 hours. Impaired renal function - prolonged.

Cycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis.|EXCRETION OF B-ALANINE & D-BETA-AMINOISOBUTYRIC ACID WAS INCR IN PT WITH TUBERCULOSIS RECEIVING CLINICAL DOSES OF D-CYCLOSERINE.|Cycloserine is inhibitory for Mycobacterium tuberculosis in concentrations of 5 to 20 ug/ml in vitro. There is no cross-resistance between cycloserine and other tuberculostatic agents. While the antibiotic is effective in experimental infections caused by other microorganisms, studies in vitro reveal no suppression of growth in cultures made in conventional media, which contain D-alanine; this amino acid blocks the antibacterial activity of cycloserine. ... Cycloserine inhibits reactions in which D-alanine is involved in bacterial cell-wall synthesis. The use of media free of D-alanine reveals that the antibiotic inhibits the growth in vitro of enterococci, E. coli, Staph. aureus, Nocardia species, and Chlamydia.

PSYCHOTIC EPISODES...ARE NEARLY ALWAYS REVERSIBLE WITHIN 2 WK, & LARGE DOSES OF CHLORPROMAZINE MAY HASTEN RECOVERY.

Limited information is available on acute overdosage of cycloserine. Symptoms of acute toxicity generally involve the CNS and include headache, vertigo, confusion, drowsiness, hyperirritability, paresthesias, dysarthria, and psychosis. Paresis, seizure, and coma may occur with large cycloserine overdosages; alcohol ingestion may increase the risk of seizures.|... Caused ill-defined visual disturbances in addition to drowsiness and mental confusion. ... Five out of 414 patients had eye symptoms consisting of flickering or feeling of pressure ... One instance of flickering vision and one of conjunctivitis /was reported/ among twenty-seven patients under treatment.

Cycloserine

Originally isolated from many Streptomyces species...now produced only synthetically.|AGRICULTURAL FUNGICIDE

GLC ASSAY DESCRIBED FOR CYCLOSERINE (4-AMINO-3-ISOXAZOLIDINONE) USING TRIMETHYLSILYL DERIVATIVES.

ATOMIC ABSORPTION SPECTROPHOTOMETRY DETERMINATION OF CYCLOSERINE IN BLOOD.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Polyketides [PK] -> Non-ribosomal peptide/polyketide hybrids [PK14]